Acute lung injury

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Acute lung injury (ALI) is a widespread, variable type of lung injury characterized by a low oxygen level in the blood (hypoxemia), non cardiogenic pulmonary edema, low lung compliance and widespread capillary leakage. ALI is caused by any event resulting in the triggering of local or systemic inflammation, principally sepsis. The term acute lung injury has been abandoned in the 2012 Berlin classification of acute respiratory distress syndrome (ARDS), and this state is now called mild ARDS. For its diagnosis, it is no longer necessary to measure pulmonary capillary wedge pressure.[1]


Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are defined as:

  • Bilateral pulmonary infiltrates on chest x-ray
  • Pulmonary Capillary Wedge Pressure < 18 mmHg (2.4 kPa)
  • PaO2/FiO2* <300 mmHg (40 kPa) = ALI
  • PaO2/FiO2 <200 mmHg (26.7 kPa)= ARDS

The patient has low lung volumes, atelectasis, loss of compliance, ventilation-perfusion mismatch (increased deadspace), and right to left shunt.

Clinical features are – severe difficulty breathing, increased rate of breathing, and resistant hypoxemia.


There are two forms of ALI. Primary ALI is caused by a direct injury to the lung (e.g., pneumonia). Secondary ALI is caused by an indirect insult (e.g. pancreatitis).

There are three phases of ALI. The acute or exudative phase is characterized by disruption of the alveolar-capillary interface, leakage of protein rich fluid into the interstitium and alveolar space, and extensive release of cytokines and migration of neutrophils. The fibroproliferative phase begins as disordered healing starts in the lungs. Cellular granulation and collagen deposition occur within the basement membrane. The pulmonary capillaries become scarred and obliterated and the alveoli become enlarged and irregularly shaped. The resolution phase occurs over several weeks as structural and vascular remodeling take place and fluid and debris are removed.


The core pathology is disruption of the capillary-endothelial interface: this actually refers to two separate barriers – the endothelium and the basement membrane of the alveolus. In the acute phase of ALI, there is increased permeability of this barrier, and protein rich fluid leaks out of the capillaries. There are two types of alveolar epithelial cells – Type 1 pneumocytes represent 90% of the cell surface area, and are easily damaged. Type 2 pneumocytes are more resistant to damage, which is important as these cells produce surfactant, transport ions and proliferate and differentiate into Type 1 cells.

The damage to the endothelium and the alveolar epithelium results in the creation of an open interface between the lung and the blood, facilitating the spread of micro-organisms from the lung systemically, stoking up a systemic inflammatory response. Moreover, the injury to epithelial cells handicaps the lung’s ability to pump fluid out of airspaces. Fluid filled airspaces, loss of surfactant, microvascular thrombosis and disorganized repair (which leads to fibrosis) reduces resting lung volumes (decreased compliance), increasing ventilation-perfusion mismatch, right to left shunt and the work of breathing. In addition, lymphatic drainage of lung units appears to be curtailed – stunned by the acute injury: this contributes to the build up of extravascular fluid.

Some patients rapidly recover from acute lung injury, and have no permanent sequelae. Prolonged inflammation and destruction of pneumocytes leads to fibroblastic proliferation, hyaline membrane formation and lung fibrosis. This fibrosing alveolitis may become apparent as early as five days after the initial injury. Subsequent recovery may be characterized by reduced physiologic reserve, and increased susceptibility to further lung injuries. Extensive microvascular thrombosis may lead to pulmonary hypertension, myocardial dysfunction and systemic hypotension.

Finally, it is essential to understand that although ALI is a diffuse process, it is also a heterogeneous process, and not all lung units are affected equally: normal and diseased tissue may exist side-by-side.


The cornerstone of treatment is to keep the PaO2 > 60 mmHg (8.0 kPa), without causing injury to the lungs with excessive O2 or volutrauma.

Pressure control ventilation (PC) is more versatile than volume control: but a volume limited strategy should be used to prevent stretch injury to the alveoli. A number of adjunct therapies are available, none have proven effective. Of these, inhaled nitric oxide and prone positioning are most frequently used. Current ventilation strategies involve using low tidal volumes with or without high levels of PEEP. The open lung approach attempts to optimize lung mechanics and minimize phasic damage by strategically placing PEEP above Pflex. Ventilator induced lung injury is caused by volutrauma and excessive use of oxygen.

Steroids may have a role in chronic ARDS in patients, without infection, with high O2 requirements days to weeks into the disease process. It was historically known as "double pneumonia".[2]

In general tidal volumes should not exceed 6ml/kg and plateau pressure should not exceed 30 cmH2O (2.9 kPa). However tidal volumes of 4ml/kg should be delivered irrespective of airway pressure. The management of patients with respiratory failure goes beyond ventilation strategies, requiring a holistic multisystem approach. Providers are reminded of the ABCDEFG mnemonic.

A = Airway, establish a patent airway, intubate as necessary.
B = Breathing, commence mechanical ventilation and obtain an adequate minute volume to maintain oxygen delivery.
C = Circulation: blood pressure, pulse, intravascular volume – fluid resuscitation and vasopressors as necessary
D = Diagnosis, find the underlying problem and control the source.
E = Empiric therapy, for example antimicrobials for sepsis
FG = Feed the Gut, to prevent villus atrophy and bacterial translocation

The principles of mechanical ventilation are simple:

  1. Give enough oxygen to keep the PaO2 over 60 mmHg (8.0 kPa) preferably, and over 50 mmHg (6.7 kPa) at the very least.
  2. Avoid volutrauma and barotrauma, by keeping the tidal volumes in the 4-6 ml/kg range and the airway plateau pressure below 30-35 cmH2O (2.9–3.4 kPa) (the tidal volume should not be less than 4ml/kg, irrespective of airway pressure).

The PaO2 is a function of the FiO2, the PEEP level, the mean airway pressure and the minute ventilation. The tidal volume, depending on what mode of ventilation is used, is determined by the pressure control level (in pressure controlled modes) or the tidal volume dialed up on the ventilator (in volume controlled modes).

There is no clear evidence that any particular mode or strategy improves outcome in ALI, except for controlling tidal volumes and airway pressures. What follows is a suggested starting strategy:

  1. Start with a high FiO2 (use the same FiO2 on the patient following intubation as before).
  2. Set the CPAP/PEEP level – if the patient has a P/F ratio of 200-300 start with CPAP/PEEP of 5 cmH2O (490 kPa), if the P/F ratio is <200, use a CPAP/PEEP of 10 cmH2O (980 kPa).
  3. For inspiratory support, use a decelerating flow pattern, with a tidal volume of 5-6 ml/kg, of if pressure control is being used, a pressure limit which gives a tidal volume of 5-6 ml/kg (1).

It is important to note that ARDS is a disease of altered lung compliance. This is reduced due to the presence of large quantities of extravascular lung water. However, chest wall compliance may also be low - in patients who are edematous, have had massive fluid resuscitation or have abdominal hypertension. In this situation, the chamber in which the lungs are inflating (the chest), bears more resemblance to a brick wall than a rib cage with muscles. Higher inflation pressures are required to inflate the lungs in these circumstances and higher PEEP is required to maintain FRC.

The choice of mode of ventilation is institution specific. The majority of intensive care units in the United States continue to use volume controlled modes of ventilation to treat ARDS. Severe hypoxemia is managed by increasing mean airway pressure by escalating levels of PEEP and rapid respiratory rates. The logic behind increasing mean airway pressure is that much of the ventilation perfusion mismatch contributing to hypoxia occurs at end expiration (click here for more information). Although the majority cases can be managed in this way, more versatile modes are available, under the pressure control umbrella.

Pressure control modes have the advantage of allowing us manipulate the mean airway pressure by prolonging inspiration, and this may improve oxygenation without increasing peak or plateau pressures . In addition, pressure control may improve gas distribution at the end of inspiration, particularly where different lung units have different resistance patterns (ALI is, after all, a heterogeneous process).

The drawback of prolonging inspiration, and, in effect, inverting the I:E ratio (2:3), is that the patient may experience a lot of discomfort, and requires deep sedation. Further, incomplete expiration tends to reduce CO2 elimination, and the patient will develop “permissive hypercapnia” and respiratory acidosis. As we now know that ventilator induced lung injury causes much more trouble than respiratory acidosis, we do not consider the latter to be a major problem (4). Newer pressure control modes such as BiLevel / Airway Pressure Release ventilation have been developed to address the problem of patient discomfort in inverse ratio ventilation; with some success.


  1. ^ (see article about ARDS)
  2. ^ Girard TD, Bernard GR (March 2007). "Mechanical ventilation in ARDS: a state-of-the-art review". Chest 131 (3): 921–9. doi:10.1378/chest.06-1515. PMID 17356115. 
  • Patrick Neligan MD (University of Pennsylvania)